Gold Nanoparticles Size Dependence on DNA Damage under X-rays

Combining gold nanoparticles (AuNPs) with 10-100 keV X-rays has shown considerable potential for radiotherapy. The uptake of AuNPs in cancer tissues is influenced by their size, with smaller sizes exhibiting enhanced penetration capabilities into deeper layers of cancer tissue compared to larger AuNPs. In this study, we examine the effect of nanoparticle (NP) size with respect to the formation of various types of DNA damage upon X-ray exposure of dried AuNP-oligo-DNA mixtures. The type and yield of DNA damage is measured using LC-MS/MS. The most important type of damage involves the release of nucleobases (Cyt > Ade ≈ Thy > Gua), which accounts for 82% of the total measured damage. The remaining 18% includes reduction products of pyrimidines (5,6-dihydrothymidine and 5,6-dihydro-2'-deoxyuridine), oxidative products (8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) and 5-hydroxymethyl-2'-deoxyuridine (5hmU)), and novel electron-specific products, including eight 2',3'- and 2',5'-dideoxynucleosides (ddNs). The presence of AuNP in close contact with DNA results in a shift of radiation-induced damage toward that mediated by electrons. Moreover, the yield of damage depends on the size of the NP, with much more damage (7-10-fold) observed for NPs with a small diameter (5 nm) compared to those with a large diameter (110 nm). The dependence of DNA damage with NP size is partly attributed to the energy of electrons emitted from the surface of AuNPs and the distance required to reach available sites of electron attachment. This study contributes to elucidate the mechanisms of AuNP radiosensitization and should aid in designing optimal NP sizes for radiotherapy.